The influence of genetic predisposition to diabetes mellitus on susceptibility to coxsackievirus B4 infection, and on virus induced pancreopathy will be studied. Dietary restriction prevents the expression of diabetes mellitus in inbred mice with recessive and dominant inheritance for diabetes, i.e., C57BL/Ks db/db -- the diabetic mutant mouse; C57BL/6J ob/ob -- the obese mouse; and the C57BL/6J Ay/a -- the yellow obese mouse, respectively. Susceptibility to coxsackievirus B4 infection in these animals under dietary restriction will be established. Similarly, coxsackievirus B4-induced pancreatic pathology during acute, convalescent, and post-convalescent stages of infection will be determined by classical histopathological techniques, special stains, and electron microscopy, with special emphasis being given to beta cell pathology. Virus localization in the pancreas of animals with diabetic heredity will be done by fluorescent antibody and peroxidase-anti-peroxidase procedures. The effects of a single and multiple episodes of viral pancreatic injury in animals with genetic predisposition to diabetes on precipitating onset of diabetes mellitus will also be ascertained. The experimental results will determine the influence of diabetogenic factors, i.e., specific mutations -- db, ob, Ay, and background modifiers -- C57BL/Ks, C57BL/6J on coxsackievirus B, (1) susceptibility, (2) pancreatic pathology, and (3) pancreopathy.